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Anemia in CKD

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https://www.readbyqxmd.com/read/29775888/therapeutic-impact-of-rhuepo-on-abnormal-platelet-app-bace-1-presenilin-1-adam-10-and-a%C3%AE-expressions-in-chronic-kidney-disease-patients-with-cognitive-dysfunction-like-alzheimer-s-disease-a-pilot-study
#1
Vinothkumar G, Krishnakumar S, Sureshkumar, Shivashekar G, Sreedhar S, Preethikrishnan, Dinesh S, Sundaram A, Balakrishnan D, Riya, Venkataraman P
BACKGROUND: Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29767854/emerging-association-between-parathyroid-hormone-and-anemia-in-hemodialysis-patients
#2
REVIEW
Motoko Tanaka, Hirotaka Komaba, Masafumi Fukagawa
Anemia is a common complication of chronic kidney disease (CKD). There are various causes of renal anemia such as decreased production of erythropoietin, resistance to erythropoietin, shortened survival of red blood cells, and bone marrow fibrosis. Secondary hyperparathyroidism (SHPT) is a less recognized, but potentially significant cause of renal anemia in CKD patients. Parathyroid hormone (PTH) has been regarded as a uremic toxin that has multiple adverse effects, and its elevated levels have been associated with renal anemia in hemodialysis patients...
May 16, 2018: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/29761242/safety-and-efficacy-of-benzbromarone-and-febuxostat-in-hyperuricemia-patients-with-chronic-kidney-disease-a-prospective-pilot-study
#3
Haibo Yu, Xinying Liu, Yaxiang Song, Jiafen Cheng, Hui Bao, Ling Qin, Xuan Zhou, Ling Wang, Ai Peng
BACKGROUND: To compare the safety and efficacy of benzbromarone and febuxostat in hyperuricemia patients with estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m2 . METHODS: This study was a single-centered, parallel-grouped, randomized clinical trial (RCT). We randomly assigned hyperuricemia participants with eGFR 20-60 mL/min/1.73 m2 into benzbromarone and febuxostat treatment group. Drugs were adjusted by titration from small doses. RESULTS: Seventy-three eligible participants enrolled, 66 subjects (33 in each group) were included finally for analysis...
May 14, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29755339/therapeutic-potential-of-a-prolyl-hydroxylase-inhibitor-fg-4592-for-parkinson-s-diseases-in-vitro-and-in-vivo-regulation-of-redox-biology-and-mitochondrial-function
#4
Xuan Li, Xin-Xin Cui, Ya-Jing Chen, Ting-Ting Wu, Huaxi Xu, Huiyong Yin, Yun-Cheng Wu
As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α) plays an important role in the pathogenesis of Parkinson's disease (PD). HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD). Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI) may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29753402/hif-activation-against-cvd-in-ckd-novel-treatment-opportunities
#5
REVIEW
Tetsuhiro Tanaka, Kai-Uwe Eckardt
Cardiovascular disease is a common and serious complication in patients with chronic kidney disease (CKD). One of the fundamental functions of the cardiovascular system is oxygen delivery, therefore cardiovascular disease inherently is linked to insufficient tissue oxygenation. Advances in our knowledge of cellular oxygen sensing by a family of prolyl hydroxylases (PHDs) and their role in regulating hypoxia-inducible factors (HIFs) have led to the discovery of PHD inhibitors as HIF stabilizers. Several small-molecule PHD inhibitors are currently in clinical trials for the treatment of anemia in CKD...
May 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29747407/transcription-factors-as-therapeutic-targets-in-chronic-kidney-disease
#6
REVIEW
Akihito Hishikawa, Kaori Hayashi, Hiroshi Itoh
The growing number of patients with chronic kidney disease (CKD) is recognized as an emerging problem worldwide. Recent studies have indicated that deregulation of transcription factors is associated with the onset or progression of kidney disease. Several clinical trials indicated that regression of CKD may be feasible via activation of the transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2), which suggests that transcription factors may be potential drug targets for CKD. Agents stabilizing hypoxia-inducible factor (HIF), which may be beneficial for renal anemia and renal protection, are also now under clinical trial...
May 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29740119/circulating-fibroblast-growth-factor-23-levels-are-associated-with-an-increased-risk-of-anemia-development-in-patients-with-nondialysis-chronic-kidney-disease
#7
Ki Heon Nam, Hyoungnae Kim, Seong Yeong An, Misol Lee, Min-Uk Cha, Jung Tak Park, Tae-Hyun Yoo, Kyu-Beck Lee, Yeong-Hoon Kim, Su-Ah Sung, Joongyub Lee, Shin-Wook Kang, Kyu Hun Choi, Curie Ahn, Seung Hyeok Han
Fibroblast growth factor-23 (FGF23) is an established biomarker of adverse outcomes in patients with chronic kidney disease (CKD). Several cross-sectional studies have suggested a possible association between FGF23 and anemia in these patients. In this large-scale prospective cohort study, we investigated this relationship and examined whether high FGF23 levels increase the risk of incident anemia. This prospective longitudinal study included 2,089 patients from the KoreaN cohort study for Outcome in patients With CKD...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29738538/the-hypoxia-inducible-factor-erythropoietin-epo-epo-receptor-pathway-is-disturbed-in-a-rat-model-of-chronic-kidney-disease-related-anemia
#8
Daniel Landau, Lital London, Inbar Bandach, Yael Segev
OBJECTIVES: Anemia is a known driver for hypoxia inducible factor (HIF) which leads to increased renal erythropoietin (EPO) synthesis. Bone marrow (BM) EPO receptor (EPOR) signals are transduced through a JAK2-STAT5 pathway. The origins of anemia of chronic kidney disease (CKD) are multifactorial, including impairment of both renal EPO synthesis as well as intestinal iron absorption. We investigated the HIF- EPO- EPOR axis in kidney, BM and proximal tibia in anemic juvenile CKD rats. METHODS: CKD was induced by 5/6 nephrectomy in young (20 days old) male Sprague-Dawley rats while C group was sham operated...
2018: PloS One
https://www.readbyqxmd.com/read/29734153/clinical-impact-of-left-ventricular-diastolic-dysfunction-in-chronic-kidney-disease
#9
Tetsuya Ogawa, Kosaku Nitta
Left ventricular diastolic dysfunction (LVDD) frequently occurs in chronic kidney disease (CKD) and is associated with heart failure and higher mortality. LVDD is observed in patients with early stages of CKD and is associated with cardiovascular events, in patients undergoing incident hemodialysis in the absence of systolic function. The pathogenesis of CKD includes abnormal ventricular filling in diastole and a higher LV filling pressure (LVFP) because of LV hypertrophy (LVH), in addition to myocardial interstitial fibrosis...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29699506/correction-to-the-ferumoxytol-for-anemia-of-ckd-trial-fact-a-randomized-controlled-trial-of-repeated-doses-of-ferumoxytol-or-iron-sucrose-in-patients-on-hemodialysis-background-and-rationale
#10
Iain C Macdougall, Naomi V Dahl, Kristine Bernard, Zhu Li, Alka Batycky, William E Strauss
Following publication of the original article [1], the authors reported that one of the authors' name is spelled incorrectly. In this Erratum the incorrect and correct author name are shown. The original publication of this article has been corrected.
April 26, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29668766/prediction-of-hemoglobin-levels-in-individual-hemodialysis-patients-by-means-of-a-mathematical-model-of-erythropoiesis
#11
Doris H Fuertinger, Franz Kappel, Hanjie Zhang, Stephan Thijssen, Peter Kotanko
Anemia commonly occurs in people with chronic kidney disease (CKD) and is associated with poor clinical outcomes. The management of patients with anemia in CKD is challenging, due to its severity, frequent hypo-responsiveness to treatment with erythropoiesis stimulating agents (ESA) and common hemoglobin cycling. Nonlinear dose-response curves and long delays in the effect of treatment on red blood cell population size complicate predictions of hemoglobin (Hgb) levels in individual patients. A comprehensive physiology based mathematical model for erythropoiesis was adapted individually to 60 hemodialysis patients treated with ESAs by identifying physiologically meaningful key model parameters from temporal Hgb data...
2018: PloS One
https://www.readbyqxmd.com/read/29666917/measurement-of-iron-status-in-chronic-kidney-disease
#12
Wesley Hayes
Anemia is a common complication of chronic kidney disease (CKD) in children, and dysregulation of iron homeostasis plays a central role in its pathogenesis. Optimizing iron status is a prerequisite for effective treatment of anemia. Insufficient iron can lead to inappropriate escalation of the erythropoiesis-stimulating agent (ESA) dose, which is associated with adverse outcomes. Excess iron supplementation also has negative sequelae including free radical tissue damage and increased risk of systemic infection...
April 17, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29659573/whole-body-iron-transport-and-metabolism-mechanistic-multi-scale-model-to-improve-treatment-of-anemia-in-chronic-kidney-disease
#13
Joydeep Sarkar, Alka A Potdar, Gerald M Saidel
Iron plays vital roles in the human body including enzymatic processes, oxygen-transport via hemoglobin and immune response. Iron metabolism is characterized by ~95% recycling and minor replenishment through diet. Anemia of chronic kidney disease (CKD) is characterized by a lack of synthesis of erythropoietin leading to reduced red blood cell (RBC) formation and aberrant iron recycling. Treatment of CKD anemia aims to normalize RBC count and serum hemoglobin. Clinically, the various fluxes of iron transport and accumulation are not measured so that changes during disease (e...
April 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29655605/physiology-and-pathophysiology-of-renal-erythropoietin-producing-cells
#14
REVIEW
Hong-Mou Shih, Chih-Jen Wu, Shuei-Liong Lin
Anemia is a common complication and contributes to increased morbidity and mortality in chronic kidney disease (CKD) patients. Whereas there has been a significant improvement of understanding the underlying mechanism of erythropoiesis, the treatment of renal anemia is still restricted to erythropoietin (EPO)-stimulating agents. The purpose of this article is to review the physiology of erythropoiesis, functional role of EPO and underlying molecular and cellular basis that regulate EPO production. Regulation of EPO production is at mRNA level...
April 11, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29604324/effect-of-blood-t1-estimation-strategy-on-arterial-spin-labeled-cerebral-blood-flow-quantification-in-children-and-young-adults-with-kidney-disease
#15
Hua-Shan Liu, Abbas F Jawad, Nina Laney, Erum A Hartung, Susan L Furth, John A Detre
PURPOSE: To compare blood T1 estimation approaches used for quantifying cerebral blood flow (CBF) with arterial spin labeled (ASL) perfusion MRI in a developmental cohort of chronic kidney disease (CKD) patients with anemia and a control group. METHODS: 61 patients with CKD and 47 age-matched control subjects were studied. Blood T1 approaches included: (1) a fixed value, (2) estimation based on measured hematocrit (Hct), and (3) estimation based on Age+Sex using a published formula...
March 28, 2018: Journal of Neuroradiology. Journal de Neuroradiologie
https://www.readbyqxmd.com/read/29593859/a-threshold-trajectory-was-revealed-by-isolating-the-effects-of-hemoglobin-rate-of-rise-in-anemia-of-chronic-kidney-disease
#16
Gregory Fusco, Ali Hariri, Carlos Vallarino, Ajay Singh, Peter Yu, Lesley Wise
Background: To assess cardiovascular risk among various hemoglobin (Hb) rates of rise (RoR) in chronic kidney disease (CKD) patients with anemia who have initiated therapy with erythropoiesis stimulating agents (ESAs). Methods: Observational cohort of CKD patients initiating ESA therapy from the Centricity® database, 1990-2011. Proportional hazards models tested the hypothesis that a slower Hb RoR (0 < g/dl/month ⩽ 0.125) is associated with a lower cardiovascular (CV) incidence [composite of fatal/nonfatal myocardial infarction (MI) and stroke] compared with faster RoR (0...
October 2017: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/29590102/common-%C3%AE-globin-variants-modify-hematologic-and-other-clinical-phenotypes-in-sickle-cell-trait-and-disease
#17
Laura M Raffield, Jacob C Ulirsch, Rakhi P Naik, Samuel Lessard, Robert E Handsaker, Deepti Jain, Hyun M Kang, Nathan Pankratz, Paul L Auer, Erik L Bao, Joshua D Smith, Leslie A Lange, Ethan M Lange, Yun Li, Timothy A Thornton, Bessie A Young, Goncalo R Abecasis, Cathy C Laurie, Deborah A Nickerson, Steven A McCarroll, Adolfo Correa, James G Wilson, Guillaume Lettre, Vijay G Sankaran, Alex P Reiner
Co-inheritance of α-thalassemia has a significant protective effect on the severity of complications of sickle cell disease (SCD), including stroke. However, little information exists on the association and interactions for the common African ancestral α-thalassemia mutation (-α3.7 deletion) and β-globin traits (HbS trait [SCT] and HbC trait) on important clinical phenotypes such as red blood cell parameters, anemia, and chronic kidney disease (CKD). In a community-based cohort of 2,916 African Americans from the Jackson Heart Study, we confirmed the expected associations between SCT, HbC trait, and the -α3...
March 28, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29581249/hypoxia-inducible-factor-prolyl-hydroxylase-inhibitor-roxadustat-fg-4592-protects-against-cisplatin-induced-acute-kidney-injury
#18
Yunwen Yang, Xiaowen Yu, Yue Zhang, Guixia Ding, Chunhua Zhu, Songming Huang, Zhanjun Jia, Aihua Zhang
Renal hypoxia occurs in acute kidney injury (AKI) of various etiologies. Activation of hypoxia-inducible transcription factor (HIF) has been identified as an important mechanism of cellular adaptation to low oxygen. Preconditional HIF activation protects against AKI, suggesting a new approach in AKI treatment. HIF is degraded under normoxic conditions mediated by oxygen-dependent hydroxylation of specific prolyl residues of the regulative α-subunits by HIF prolyl hydroxylases (PHD). FG-4592 is a novel, orally active small-molecule HIF PHD inhibitor for the treatment of anemia in patients with CKD...
March 26, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29569190/hif-stabilizers-in-the-management-of-renal-anemia-from-bench-to-bedside-to-pediatrics
#19
REVIEW
Dalvir Kular, Iain C Macdougall
Anemia is a common complication of chronic kidney disease (CKD) in adult and pediatric patients. It has traditionally been treated with erythropoietin therapy and iron supplementation, with great success. With the discovery of the major transcription factor hypoxia inducible factor (HIF) for the erythropoietin gene in 1992, molecules were created that inhibit the HIF prolyl-hydroxylase enzyme. This new class of drug-called HIF stabilizers, or HIF prolyl-hydroxylase inhibitors-prevents the proteasomal degradation of HIF-α, thereby inducing upregulation of the erythropoietin gene...
March 22, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29554879/epidemiology-and-risk-factors-in-ckd-patients-with-pulmonary-hypertension-a-retrospective-study
#20
Qian Zhang, Le Wang, Hongbing Zeng, Yongman Lv, Yi Huang
BACKGROUND: Pulmonary hypertension (PH) is a rare disease often associated with high mortality and is recently recognized as a common complication secondary to chronic kidney disease (CKD). Epidemiological data for this disorder across the spectrum of CKD is poorly understood. METHODS: We retrospectively analyzed 705 CKD patients with complete clinical records from July 2013 to September 2015. All the patients were estimated by echocardiography and PH was defined as pulmonary artery systolic pressure (PASP) > 35 mmHg...
March 20, 2018: BMC Nephrology
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